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ABSTRACT

Background Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined.

Methods We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined.

Results After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P=0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33).

Conclusions Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.

Methods

Study Design

Subjects with type 2 diabetes mellitus 18 to 80 years of age who had been receiving maintenance hemodialysis for less than two years were enrolled at 178 centers in Germany. Exclusion criteria included levels of fasting serum low-density lipoprotein (LDL) cholesterol of less than 80 mg per deciliter (2.1 mmol per liter) or more than 190 mg per deciliter (4.9 mmol per liter), triglyceride levels greater than 1000 mg per deciliter (11.3 mmol per liter); liver-function values more than three times the upper limit of normal or equal to those in patients with symptomatic hepatobiliary cholestatic disease; hematopoietic disease or systemic disease unrelated to end-stage renal disease; vascular intervention, congestive heart failure, or myocardial infarction within the three months preceding the period of enrollment; unsuccessful kidney transplantation; and hypertension resistant to therapy (i.e., systolic blood pressure continuously greater than 200 mm Hg or diastolic blood pressure greater than 110 mm Hg). On enrollment, lipid-lowering medications were discontinued, and patients received placebo during the four-week run-in phase of the study. Thereafter, eligible patients were randomly assigned to double-blind treatment with either atorvastatin at a dose of 20 mg once daily or matching placebo. Data were recorded at four weeks and then every six months. The protocol was approved by the ethics committee at the coordinating center and the 29 regional institutional review boards. Specifically, the ethical implications of the inclusion of a placebo group — that is, of not providing lipid-lowering medications to those randomly assigned to the control group — were taken into account and considered acceptable. Written informed consent was obtained from all patients.

Academic investigators led, managed, and coordinated the study. The principal investigators wrote the protocol and prepared the manuscript. The data were monitored and collected by two contract research organizations supported by Pfizer, one of which (Datamap) holds the data. A university-based, independent statistician performed the statistical analyses. The plan for the statistical analysis was completed before the database was locked and unblinded.

A computer-generated randomization code was prepared by a central Pfizer unit that was independent of local study personnel. Medication was prepackaged on the basis of a block size of four subjects at each center. Each consecutive subject was given the next consecutive randomization number, and eligible patients were assigned in a 1:1 ratio to receive the study drug or placebo. Lipid levels measured after randomization were not released to the clinical sites. If LDL cholesterol levels fell below 50 mg per deciliter (1.3 mmol per liter), the dose of atorvastatin was reduced to 10 mg per day. To maintain blinding, a randomly selected subject from the placebo group received an identical dose reduction. One person in the central laboratory who had access to the randomization code controlled the changes in dose. After a patient reached a primary end point, the study drug could be replaced by treatment with an active statin. Details of the study design have been described previously.^12,13

End Points

The study end points and serious adverse events were continuously monitored and reported to the contract research organization. Every end point was adjudicated by three members of the end-point committee, on the basis of predefined criteria that are part of the study protocol. All analyses of primary and secondary end points were based on the classification by the end-point committee that was agreed on by consensus or majority vote. All committee members were blinded to the treatment assignments until August 13, 2004. The primary end point was a composite of death from cardiac causes, fatal stroke, nonfatal myocardial infarction, or nonfatal stroke, whichever occurred first. Only one event per subject was included in the analysis. Myocardial infarction was diagnosed when two of the following three criteria were met: typical symptoms; elevated levels of cardiac enzymes (i.e., a level of creatine kinase MB above 5 percent of the total level of creatine kinase, a level of lactic dehydrogenase 1.5 times the upper limit of normal, or a level of troponin T greater than 2 ng per milliliter); or diagnostic changes on the electrocardiogram. A resting electrocardiogram was recorded every six months and evaluated by independent cardiologists from the electrocardiographic monitoring board, according to the Minnesota classification system for the electrocardiogram (codes 1-1-1 through 9-2 for QRS-complex, ST-segment, or T-wave changes). An electrocardiogram that documented silent myocardial infarction was considered evidence of a primary end point.

Stroke was defined as a neurologic deficit lasting longer than 24 hours. Computed tomographic or magnetic resonance imaging of the brain was recommended and available in all but 16 cases. Death from cardiac causes comprised fatal myocardial infarction (death within 28 days after a myocardial infarction), sudden death, death due to congestive heart failure, death due to coronary heart disease during or within 28 days after an intervention, and all other deaths ascribed to coronary heart disease. Patients who died unexpectedly and did not present with a potassium level greater than 7.5 mmol per liter before the start of the three most recent sessions of hemodialysis were considered to have had sudden death from cardiac causes.

Secondary end points included death from all causes, all cardiac events combined, and all cerebrovascular events combined. Death from any cause other than cardiac disease or cerebrovascular disease was treated as a competing risk.

A central laboratory performed all the analyses. LDL cholesterol was measured directly by agarose-gel electrophoresis with subsequent enzymatic staining for cholesterol with the use of the rapid electrophoresis system (Helena Diagnostika). This method produces more accurate measurements of LDL cholesterol than ultracentrifugation and precipitation combined in samples with elevated triglyceride concentrations.¹⁴

Statistical Analysis

The study was designed to have 90 percent power to detect a 27 percent reduction in the incidence of the composite primary end point at an alpha level of 0.05 in a two-sided test, adjusted for one preplanned interim analysis according to an alpha-spending function based on the O'Brien–Fleming method, yielding a nominal level of significance for the final analysis of 0.045.¹⁵ The alpha-spending function would have allowed for additional interim analyses, if necessary. For the study to have this level of power, at least 424 primary end points had to occur (event-driven analysis), requiring the randomization of at least 1200 patients. This calculation was based on observational studies.^16,17 The results were assessed in an intention-to-treat analysis. The primary end points were evaluated according to time-to-event analysis. Death from other causes was treated as a competing event, and for patients who died from other causes, follow-up was censored as of the date of death.¹⁸ Times to an event for patients without a primary end point or competing event were treated as censored and were calculated as the time from randomization to the date of the last contact.

Cumulative incidence and Kaplan–Meier curves were used only to show the survival curves within the treatment groups and to calculate the corresponding survival probabilities. The Cox proportional-hazards model was used to estimate the multivariate relative risks of the primary and secondary end points with corresponding 95 percent confidence intervals. Adjustments were made for sex, age, and baseline status with respect to coronary heart disease. Unless otherwise stated, the baseline lipid and safety laboratory value was defined as the last value measured during the run-in period. The baseline data were analyzed with the use of standard descriptive statistics.

Results

Patients

A total of 1255 subjects were randomly assigned to double-blind treatment with either atorvastatin (619) or placebo (636) between March 1998 and October 2002 and were followed until their final visit in March 2004 (Figure 1). The two groups of patients were well matched with respect to baseline characteristics and concomitant therapy (Table 1). Nineteen percent of the patients had taken statins before entering the study. The mean length of follow-up was 3.96 years in the atorvastatin group and 3.91 years in the placebo group (median, 4.0 and 4.08 years, respectively).

View larger version (30K): [in this window] [in a new window]   Figure 1. Numbers of Patients Who Entered the Study, Were Assigned to a Study Group, and Completed the Protocol.

 

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics of Patients in the Placebo and Atorvastatin Groups.

 
Lipid Levels

At randomization, the median level of LDL cholesterol was 121 mg per deciliter (3.13 mmol per liter) in the atorvastatin group and 125 mg per deciliter (3.23 mmol per liter) in the placebo group. After four weeks, in the atorvastatin group, the median level of LDL cholesterol was 72 mg per deciliter (1.86 mmol per liter; median change from baseline, –42 percent). In the placebo group, the level of LDL cholesterol remained essentially unchanged (120 mg per deciliter [3.10 mmol per liter]; median change from baseline, –1.3 percent) (Figure 2).

View larger version (16K): [in this window] [in a new window]   Figure 2. Median Level of Low-Density Lipoprotein (LDL) Cholesterol from Baseline to the End of the Study. To convert values for LDL cholesterol to millimoles per liter, multiply by 0.02586.

 
Primary Outcomes

The cumulative incidence of the primary end point was 12.6 percent at one year and 31.9 percent at three years in the atorvastatin group, as compared with 11.2 percent and 30.5 percent, respectively, in the placebo group (Figure 3). The relative risk reduction afforded by active treatment, as compared with placebo, was 8 percent (hazard ratio, 0.92; 95 percent confidence interval, 0.77 to 1.10; P=0.37). A similar number of patients died from cardiac causes in the two groups (20 percent in the atorvastatin group and 23 percent in the placebo group; relative risk, 0.81; 95 percent confidence interval, 0.64 to 1.03; P=0.08). Eleven percent (70) of the patients in the atorvastatin group had a nonfatal myocardial infarction, as compared with 12 percent (79) of those in the placebo group (relative risk, 0.88; 95 percent confidence interval, 0.64 to 1.21; P=0.42). More patients (27) died of stroke in the atorvastatin group than in the placebo group (13; relative risk, 2.03; 95 percent confidence interval, 1.05 to 3.93; P=0.04). Nonfatal stroke was distributed equally in the two groups (33 patients in the atorvastatin group and 32 patients in the placebo group; relative risk, 1.04; 95 percent confidence interval, 0.64 to 1.69; P=0.89) (Table 2).

View larger version (18K): [in this window] [in a new window]   Figure 3. Estimated Cumulative Incidence of the Composite Primary End Point.

 

View this table: [in this window] [in a new window]   Table 2. Rates of Primary and Secondary End Points.

 
Secondary Outcomes

Death from all causes was similar in the two groups (48 percent in the atorvastatin group, as compared with 50 percent in the placebo group; relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P=0.33). Of nominal significance, the risk of all cardiac events combined was reduced by 18 percent in the atorvastatin group, with a total event rate of 33 percent, as compared with 39 percent in the placebo group (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P=0.03) (Table 2). This result was driven mainly by differences in the rates of coronary-artery bypass grafting and percutaneous transluminal coronary angioplasty. The incidence of all cerebrovascular events combined in the atorvastatin group was not different from that in the placebo group (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P=0.49) (Table 2).

Adherence, Tolerability, and Adverse Events

The mean (±SD) duration of exposure to placebo was 27.2±17.9 months (range, 0.03 to 70.2), and to atorvastatin, 28.5±18.6 months (range, 0.07 to 69.9). In the placebo group, 82 percent of patients took the study medication without interruption, and in the atorvastatin group, 80 percent of patients did so. The average number of days that treatment was interrupted was 12±36 in the placebo group and 13±40 in the atorvastatin group. During treatment, the dose of atorvastatin or matching placebo was halved when administered to 190 patients (15 percent). During the study, 98 patients in the placebo group (15 percent) began nonstudy statins, as compared with 10 percent of those in the atorvastatin group. The proportion of patients who continued to receive the study drug at one and two years, expressed as a percentage of those who remained alive and free of a primary event, was 74 percent (459 patients) and 51 percent (317 patients), respectively, in the atorvastatin group and 74 percent (469 patients) and 48 percent (303 patients), respectively, in the placebo group.

Patients receiving hemodialysis generally have many adverse and serious adverse events (Table 3), but no cases of rhabdomyolysis or severe liver disease were detected in either group. The study medication was discontinued by the investigators in one patient receiving placebo because of a report of myalgia in combination with elevated creatine kinase levels.

View this table: [in this window] [in a new window]   Table 3. Adverse Events.

 
Discussion

We examined the value of lowering the level of LDL cholesterol in patients receiving hemodialysis who have type 2 diabetes mellitus, among whom the average annual incidence of myocardial infarction or death from coronary heart disease is 8.2 percent. This incidence rate exceeds the average annual rates of major coronary events that were reported in the placebo group of the Scandinavian Simvastatin Survival Study (6.6 percent) and is the highest rate of cardiovascular events in a long-term prospective trial of statin therapy.¹⁹ Atorvastatin (20 mg daily) lowered LDL cholesterol levels by 42 percent, to 72 mg per deciliter, which is close to the target value of 70 mg per deciliter (1.81 mmol per liter) recommended by the Third Adult Treatment Panel of the National Cholesterol Education Program for persons at very high risk of cardiovascular disease. Despite the high rate of cardiovascular events and the pronounced LDL cholesterol–lowering activity of atorvastatin, a significant reduction in the incidence of the composite primary end point was not achieved.

Of nominal significance, more cases of fatal stroke occurred in the atorvastatin group (27) than in the placebo group (13). This finding is unexplained and could be a chance finding, particularly in view of the data from CARDS, which indicate that atorvastatin lowers the incidence of stroke.³ That study reported a relative risk for stroke of 0.52 (95 percent confidence interval, 0.31 to 0.89) in persons with type 2 diabetes mellitus who were taking atorvastatin. The rate of fatal and nonfatal stroke decreased from 2.8 to 1.5 percent (39 vs. 21 patients), whereas in the present study, it increased from 7.0 to 9.7 percent (44 vs. 59 patients).

The complete absence of a stroke benefit and the increase in fatal strokes contribute considerably to the finding that the treatment effect on the primary end point was less than predicted. A possible reason for the unexpected results with regard to the primary end point might be related to the LDL cholesterol concentration at baseline. In general, the absolute risk reduction attained by lowering LDL cholesterol by a given percentage is less when pretreatment concentrations are low than when they are high.²⁰ The baseline levels of LDL cholesterol among patients in our study were, on average, above the target (126 mg per deciliter [3.25 mmol per liter]). Given the log-linear relation between LDL cholesterol and coronary heart disease, reducing levels of LDL cholesterol by 40 percent from a starting level of 125 mg per deciliter would result in an approximate relative risk reduction of 30 percent or more.²⁰ This estimate is empirically supported by the results of CARDS³ and the British Heart Protection Study²¹ and is very close to our initial assumption of a risk reduction of 27 percent.

Since we did not fully achieve this benefit, we speculate that the pathogenesis of vascular events in patients with diabetes mellitus who are receiving hemodialysis may, at least in part, be different from that in patients without end-stage renal disease. Subgroup analyses showed no difference in outcome for any LDL cholesterol level or patients with and patients without cardiovascular disease. Interestingly, there was a continuous decrease in LDL cholesterol levels over time among patients in both groups. Some malnutrition cannot be ruled out during the course of the study, although there was no decrease in the body-mass index.

The extremely high rate of death from cardiovascular causes among patients receiving dialysis²² is explained by more than the traditional coronary risk factors. Apart from the presence of many aggravating coexisting factors, such as inappropriate left ventricular hypertrophy, cardiac fibrosis, cardiac microvessel disease,²³ and sympathetic overactivity, among others, there are also indications that atherosclerosis itself is promoted by risk factors other than the traditional cardiovascular risk factors.^24,25 The most plausible explanation for the absence of a significant effect on mortality from cardiac causes and cardiac end points in this study is the presence of additional pathogenetic pathways in cardiovascular disease. The dose of atorvastatin in the present study was 20 mg, which is lower than the high dose used in a recent study by LaRosa et al.²⁶ in which intensive lipid-lowering therapy with atorvastatin at a dose of 80 mg per day was more effective than a dose of 10 mg per day in patients with stable coronary heart disease. However, whether such an advantage would accrue if patients with type 2 diabetes who were receiving dialysis were given a higher dose of atorvastatin is unknown.

Several important conclusions can be drawn from this study. First, we showed that it is difficult to rely on uncontrolled observational studies that show substantial advantages of statins in the treatment of patients receiving hemodialysis.^9,27 Second, and more important, is the conclusion that the benefit of atorvastatin is limited when intervention with statins is postponed until patients have reached end-stage renal disease. Subgroup analyses of major statin-intervention trials documented a cardiovascular benefit in patients with chronic kidney disease (stages 1, 2, and 3 according to the classification of the National Kidney Foundation).^28,29 According to CARDS, lowering LDL cholesterol levels early during the clinical course of type 2 diabetes mellitus is of benefit.³ Third, there was no excess of serious adverse events; specifically, no cases of rhabdomyolysis occurred, but we found a nominally significant increase in fatal stroke.

We conclude that in persons with type 2 diabetes mellitus who are receiving maintenance hemodialysis and have LDL cholesterol values between 80 and 190 mg per deciliter, routine treatment with a statin to reduce the primary composite end point of death from cardiac causes, myocardial infarction, and stroke is not warranted. The initiation of lipid-lowering therapy in patients with type 2 diabetes mellitus who already have end-stage renal disease may come too late to translate into consistent improvement of the cardiovascular outcome.

Supported by Pfizer. The committee members and investigators did not receive remuneration for conducting the study, except for reimbursement of costs to participate in scientific meetings.

Dr. Wanner reports having received consulting fees and lecture fees from Genzyme; Dr. März, consulting fees, lecture fees, a research grant and stock options from Pfizer; and Dr. Mann, lecture fees from Aventis, Roche, and Janssen Cilag. Dr. Ritz is a member of the safety board of a trial sponsored by AstraZeneca and reports having received consulting fees from the company.

We are indebted to the German Association for Clinical Nephrology (K.-W. Kühn, chair) and the Association of German Nephrology Centers (H. Kütemeyer, chair).

^* Investigators and research coordinators participating in this study are listed in the Appendix.

Source Information

From the Department of Medicine, Division of Nephrology, University of Würzburg, Würzburg, Germany (C.W., V.K.); the Clinical Institute of Medical and Chemical Laboratory Diagnostics, University General Hospital, Graz, Austria (W.M.); the Department of Medical Biometrics and Statistics, University Hospital of Freiburg, Freiburg, Germany (M.O.); Schwabing General Hospital, Munich, Germany (J.F.E.M.); Clinical Research Department, Pfizer, Karlsruhe, Germany (G.R.); and the Department of Medicine, University of Heidelberg, Heidelberg, Germany (E.R.).

Address reprint requests to Dr. Wanner at the Department of Medicine, Division of Nephrology, University Hospital, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany, or at wanner_c{at}medizin.uni-wuerzburg.de.

References

1. Cheung BM, Lauder IJ, Lau CP, Kumana CR. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br J Clin Pharmacol 2004;57:640-651. [CrossRef][ISI][Medline]
2. Armitage J, Bowman L. Cardiovascular outcomes among participants with diabetes in the recent large statin trials. Curr Opin Lipidol 2004;15:439-446. [CrossRef][Medline]
3. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685-696. [CrossRef][ISI][Medline]
4. Schwenger V, Hofmann A, Kalifeh N, et al. Uremic patients -- late referral, early death. Dtsch Med Wochenschr 2003;128:1216-1220. [Medline]
5. Koch M, Thomas B, Tschöpe W, Ritz E. Survival and predictors of death in dialysed diabetic patients. Diabetologia 1993;36:1113-1117. [CrossRef][ISI][Medline]
6. Renal Data System. USRDS 2003 annual data report: atlas of end-stage renal disease in the United States. Bethesda, Md.: National Institute of Diabetes and Digestive and Kidney Disease, 2003. (Accessed June 27, 2005, at http://www.usrds.org.)
7. Prichard SS. Impact of dyslipidemia in end-stage renal disease. J Am Soc Nephrol 2003;14:Suppl 4:S315-S320. [Free Full Text]
8. Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002;61:1887-1893. [CrossRef][ISI][Medline]
9. Seliger SL, Weiss NS, Gillen DL, et al. HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int 2002;61:297-304. [CrossRef][ISI][Medline]
10. Baigent C, Burbury K, Wheeler D. Premature cardiovascular disease in chronic renal failure. Lancet 2000;356:147-152. [CrossRef][ISI][Medline]
11. Lins RL, Matthys KE, Verpooten GA, et al. Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients. Nephrol Dial Transplant 2003;18:967-976. [Free Full Text]
12. Wanner C, Krane V, Ruf G, März W, Ritz E. Rationale and design of a trial improving outcome of type 2 diabetics on hemodialysis. Kidney Int Suppl 1999;71:S222-S226. [Medline]
13. Wanner C, Krane V, März W, et al. Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D Study): demographic and baseline characteristics. Kidney Blood Press Res 2004;27:259-266. [CrossRef][ISI][Medline]
14. Nauck M, Winkler K, März W, Wieland H. Quantitative determination of high-, low-, and very-low-density lipoproteins and lipoprotein(a) by agarose gel electrophoresis and enzymatic cholesterol staining. Clin Chem 1995;41:1761-1767. [Abstract]
15. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549-556. [CrossRef][ISI][Medline]
16. Tschöpe W, Koch M, Thomas B, Ritz E. Serum lipids predict cardiac death in diabetic patients on maintenance hemodialysis: results of a prospective study. Nephron 1993;64:354-358. [ISI][Medline]
17. Koch M, Kuthuhn B, Trenkwalder E, et al. Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients. J Am Soc Nephrol 1997;8:1889-1898. [Abstract]
18. Schulgen G, Olschewski M, Krane V, Wanner C, Ruf G, Schumacher M. Sample sizes for clinical trials with time-to-event endpoints and competing risks. Contemp Clin Trials 2005;26:386-396. [Medline]
19. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-1389. [CrossRef][ISI][Medline]
20. Grundy SM, Cleeman JI, Merz CNB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-239. [Erratum, Circulation 2004;110:763.] [CrossRef][ISI][Medline]
21. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22. [CrossRef][ISI][Medline]
22. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:Suppl 3:S112-S119. [ISI][Medline]
23. Amann K, Breitbach M, Ritz E, Mall G. Myocyte/capillary mismatch in the heart of uremic patients. J Am Soc Nephrol 1998;9:1018-1022. [Abstract]
24. Takayama F, Aoyama I, Tsukushi S, et al. Immunohistochemical detection of imidazolone and N(epsilon)-(carboxymethyl) lysine in aortas of hemodialysis patients. Cell Mol Biol 1998;44:1101-1109. [Medline]
25. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int 2002;62:1524-1538. [CrossRef][ISI][Medline]
26. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-1435. [Free Full Text]
27. Mason NA, Bailie GR, Satayathum S, et al. HMG-coenzyme A reductase inhibitor use is associated with mortality reduction in hemodialysis patients. Am J Kidney Dis 2005;45:119-126. [CrossRef][Medline]
28. Tonelli M, Isles C, Curhan GC, et al. Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation 2004;110:1557-1563. [CrossRef][ISI][Medline]
29. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:Suppl 1:S1-S266. [CrossRef][ISI][Medline]

The following investigators and research coordinators participated in the study known as the 4D Study (a complete list is available at www.uni-wuerzburg.de/nephrologie): Steering committee: C. Wanner, E. Ritz. Clinical coordinator: V. Krane. Medical end-point monitors: Z. Ülger, F. Swoboda. Data and safety monitoring committee: M. Wehling (chair), E. Keller (deceased), M. Schumacher, T. Eschenhagen. Event committee: J. Mann (chair), J. Bommer, P. Schanzenbächer, P. Schollmeyer, M. Schartl. Electrocardiography monitoring board: F. Heinrich, H. Mörl. Biometric and statistical analysis: University of Freiburg, M. Olschewski. Central laboratory (lipid and safety core laboratory): University of Freiburg, W. März. Contract research organization: Kendle, Munich, S. Reichmuth (Project manager); Datamap, Freiburg, J. Lilienthal. Sponsor: Pfizer, Karlsruhe, G. Ruf, B. Rauer (Project manager).

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Related Letters:

Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Dialysis
Langer A., Robinson J. G., Jaber B. L., Madias N. E., Wanner C., Krane V., Ritz E.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:1858-1860, Oct 27, 2005. Correspondence

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• Yang, X., So, W. Y., Ma, R., Ko, G., Kong, A., Lam, C., Ho, C. S., Cockram, C., Chow, C.-C., Tong, P., Chan, J. (2008). Effects of albuminuria and renal dysfunction on development of dyslipidaemia in type 2 diabetes--the Hong Kong Diabetes Registry. Nephrol Dial Transplant 0: gfn149v1-gfn149 [Abstract] [Full Text]  
• Strippoli, G. F M, Navaneethan, S. D, Johnson, D. W, Perkovic, V., Pellegrini, F., Nicolucci, A., Craig, J. C (2008). Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials. BMJ 336: 645-651 [Abstract] [Full Text]  
• Schlieper, G., Hristov, M., Brandenburg, V., Kruger, T., Westenfeld, R., Mahnken, A. H., Yagmur, E., Boecker, G., Heussen, N., Gladziwa, U., Ketteler, M., Weber, C., Floege, J. (2008). Predictors of low circulating endothelial progenitor cell numbers in haemodialysis patients. Nephrol Dial Transplant 0: gfn103v1-gfn103 [Abstract] [Full Text]  
• Stenvinkel, P., Carrero, J. J., Axelsson, J., Lindholm, B., Heimburger, O., Massy, Z. (2008). Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient: How Do New Pieces Fit into the Uremic Puzzle?. CJASN 3: 505-521 [Abstract] [Full Text]  
• Herzog, C. A., Strief, J. W., Collins, A. J., Gilbertson, D. T. (2008). Cause-specific mortality of dialysis patients after coronary revascularization: why don't dialysis patients have better survival after coronary intervention?. Nephrol Dial Transplant 0: gfn038v1-gfn038 [Abstract] [Full Text]  
• Richards, N., Harris, K., Whitfield, M., O'Donoghue, D., Lewis, R., Mansell, M., Thomas, S., Townend, J., Eames, M., Marcelli, D. (2008). Primary care-based disease management of chronic kidney disease (CKD), based on estimated glomerular filtration rate (eGFR) reporting, improves patient outcomes. Nephrol Dial Transplant 23: 549-555 [Abstract] [Full Text]  
• American College of Cardiology/American Heart Asso, , 2007 Writing Group to Review New Evidence and Upda, , King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. J Am Coll Cardiol 51: 172-209 [Full Text]  
• King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O., 2005 WRITING COMMITTEE MEMBERS, , Smith, S. C. Jr, Feldman, T. E., Hirshfeld, J. W. Jr, Jacobs, A. K., Kern, M. J., King, S. B. III, Morrison, D. A., O'Neill, W. W., Schaff, H. V., Whitlow, P. L., Williams, D. O., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Buller, C. E., Creager, M. A., Ettinger, S. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B., Tarkington, L. G., Yancy, C. W. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee. Circulation 117: 261-295 [Full Text]  
• Garg, A. X., Greene, T., Levin, N. W. (2008). A well-conducted randomized trial that establishes no benefit of therapy is an important medical advance. Nephrol Dial Transplant 23: 52-55 [Full Text]  
• Novak, J. E., Szczech, L. A. (2008). Feast and Famine: Epidemiology and Clinical Trials in Chronic Kidney Disease. J. Am. Soc. Nephrol. 19: 2-4 [Full Text]  
• Joy, M. S, Dornbrook-Lavender, K. A, Chin, H., Hogan, S. L, Denu-Ciocca, C. (2008). Effects of Atorvastatin on Lp(a) and Lipoprotein Profiles in Hemodialysis Patients. The Annals of Pharmacotherapy 42: 9-15 [Abstract] [Full Text]  
• Kessler, M., Zannad, F., Lehert, P., Grunfeld, J. P., Thuilliez, C., Leizorovicz, A., Lechat, P., for the FOSIDIAL Investigators, (2007). Predictors of cardiovascular events in patients with end-stage renal disease: an analysis from the Fosinopril in Dialysis study. Nephrol Dial Transplant 22: 3573-3579 [Abstract] [Full Text]  
• Henyan, N. N, Riche, D. M, East, H. E, Gann, P. N (2007). Impact of Statins on Risk of Stroke: A Meta-Analysis. The Annals of Pharmacotherapy 41: 1937-1945 [Abstract] [Full Text]  
• Khawar, O., Kalantar-Zadeh, K., Lo, W. K., Johnson, D., Mehrotra, R. (2007). Is the Declining Use of Long-Term Peritoneal Dialysis Justified by Outcome Data?. CJASN 2: 1317-1328 [Abstract] [Full Text]  
• Khella, S., Bleicher, M. B. (2007). Stroke and Its Prevention in Chronic Kidney Disease. CJASN 2: 1343-1351 [Abstract] [Full Text]  
• Romayne Kurukulasuriya, L., Athappan, G., Saab, G., Whaley Connell, A., Sowers, J. R. (2007). Review: HMG CoA reductase inhibitors and renoprotection: the weight of the evidence. Therapeutic Advances in Cardiovascular Disease 1: 49-59 [Abstract]  
• Macdougall, I. C., Eckardt, K.-U., Locatelli, F. (2007). Latest US KDOQI Anaemia Guidelines update what are the implications for Europe?. Nephrol Dial Transplant 22: 2738-2742 [Full Text]  
• Foley, R. N., Collins, A. J. (2007). End-Stage Renal Disease in the United States: An Update from the United States Renal Data System. J. Am. Soc. Nephrol. 18: 2644-2648 [Abstract] [Full Text]  
• Culleton, B. F., Walsh, M., Klarenbach, S. W., Mortis, G., Scott-Douglas, N., Quinn, R. R., Tonelli, M., Donnelly, S., Friedrich, M. G., Kumar, A., Mahallati, H., Hemmelgarn, B. R., Manns, B. J. (2007). Effect of Frequent Nocturnal Hemodialysis vs Conventional Hemodialysis on Left Ventricular Mass and Quality of Life: A Randomized Controlled Trial. JAMA 298: 1291-1299 [Abstract] [Full Text]  
• Jamison, R. L., Hartigan, P., Kaufman, J. S., Goldfarb, D. S., Warren, S. R., Guarino, P. D., Gaziano, J. M., For the Veterans Affairs Site Investigators, (2007). Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease: A Randomized Controlled Trial. JAMA 298: 1163-1170 [Abstract] [Full Text]  
• Glynn, L. G., Reddan, D., Newell, J., Hinde, J., Buckley, B., Murphy, A. W. (2007). Chronic kidney disease and mortality and morbidity among patients with established cardiovascular disease: a West of Ireland community-based cohort study. Nephrol Dial Transplant 22: 2586-2594 [Abstract] [Full Text]  
• Kalantar-Zadeh, K. (2007). Inflammatory Marker Mania in Chronic Kidney Disease: Pentraxins at the Crossroad of Universal Soldiers of Inflammation. CJASN 2: 872-875 [Full Text]  
• Chertow, G. M., Pupim, L. B., Block, G. A., Correa-Rotter, R., Drueke, T. B., Floege, J., Goodman, W. G., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Albizem, M., Olson, K., Klassen, P., Parfrey, P. (2007). Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): Rationale and Design Overview. CJASN 2: 898-905 [Abstract] [Full Text]  
• Bleyer, A. J. (2007). Use of Antimicrobial Catheter Lock Solutions to Prevent Catheter-Related Bacteremia. CJASN 2: 1073-1078 [Abstract] [Full Text]  
• Chen, Y., Ruan, X. Z., Li, Q., Huang, A., Moorhead, J. F., Powis, S. H., Varghese, Z. (2007). Inflammatory cytokines disrupt LDL-receptor feedback regulation and cause statin resistance: a comparative study in human hepatic cells and mesangial cells. Am. J. Physiol. Renal Physiol. 293: F680-F687 [Abstract] [Full Text]  
• Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50: e1-e157 [Full Text]  
• Cavanaugh, K. L. (2007). Diabetes Management Issues for Patients With Chronic Kidney Disease. Clin. Diabetes 25: 90-97 [Abstract] [Full Text]  
• DeLoach, S. S., Mohler, E. R. III (2007). Peripheral Arterial Disease: A Guide for Nephrologists. CJASN 2: 839-846 [Abstract] [Full Text]  
• Nogueira, J., Weir, M. (2007). The Unique Character of Cardiovascular Disease in Chronic Kidney Disease and Its Implications for Treatment with Lipid-Lowering Drugs. CJASN 2: 766-785 [Abstract] [Full Text]  
• Nanayakkara, P. W. B., van Guldener, C., ter Wee, P. M., Scheffer, P. G., van Ittersum, F. J., Twisk, J. W., Teerlink, T., van Dorp, W., Stehouwer, C. D. A. (2007). Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease: Results From the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med 167: 1262-1270 [Abstract] [Full Text]  
• Pun, P. H., Lehrich, R. W., Smith, S. R., Middleton, J. P. (2007). Predictors of Survival after Cardiac Arrest in Outpatient Hemodialysis Clinics. CJASN 2: 491-500 [Abstract] [Full Text]  
• Herzog, C. A. (2007). Can We Prevent Sudden Cardiac Death in Dialysis Patients?. CJASN 2: 410-412 [Full Text]  
• Bro, S., Binder, C. J., Witztum, J. L., Olgaard, K., Nielsen, L. B. (2007). Inhibition of the Renin-Angiotensin System Abolishes the Proatherogenic Effect of Uremia in Apolipoprotein E-Deficient Mice. Arterioscler. Thromb. Vasc. Bio. 27: 1080-1086 [Abstract] [Full Text]  
• Kalantar-Zadeh, K., Kilpatrick, R. D., McAllister, C. J., Miller, L. G., Daar, E. S., Gjertson, D. W., Kopple, J. D., Greenland, S. (2007). Hepatitis C Virus and Death Risk in Hemodialysis Patients. J. Am. Soc. Nephrol. 18: 1584-1593 [Abstract] [Full Text]  
• Gupta, R., Plantinga, L. C., Fink, N. E., Melamed, M. L., Coresh, J., Fox, C. S., Levin, N. W., Powe, N. R. (2007). Statin Use and Hospitalization for Sepsis in Patients With Chronic Kidney Disease. JAMA 297: 1455-1464 [Abstract] [Full Text]  
• Zhu, X.-Y., Daghini, E., Chade, A. R., Napoli, C., Ritman, E. L., Lerman, A., Lerman, L. O. (2007). Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs. J. Am. Soc. Nephrol. 18: 1209-1217 [Abstract] [Full Text]  
• Kwan, B. C.H., Kronenberg, F., Beddhu, S., Cheung, A. K. (2007). Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease. J. Am. Soc. Nephrol. 18: 1246-1261 [Full Text]  
• Himmelfarb, J., Henrich, W., DuBose, T. (2007). Anemia of Kidney Disease and Clinical Practice Guidelines: Quo Vadis?. CJASN 2: 213-214 [Full Text]  
• Lehrich, R. W., Pun, P. H., Tanenbaum, N. D., Smith, S. R., Middleton, J. P. (2007). Automated External Defibrillators and Survival from Cardiac Arrest in the Outpatient Hemodialysis Clinic. J. Am. Soc. Nephrol. 18: 312-320 [Abstract] [Full Text]  
• Kovesdy, C. P., Anderson, J. E., Kalantar-Zadeh, K. (2007). Inverse Association between Lipid Levels and Mortality in Men with Chronic Kidney Disease Who Are Not Yet on Dialysis: Effects of Case Mix and the Malnutrition-Inflammation-Cachexia Syndrome. J. Am. Soc. Nephrol. 18: 304-311 [Abstract] [Full Text]  
• Kilpatrick, R. D., McAllister, C. J., Kovesdy, C. P., Derose, S. F., Kopple, J. D., Kalantar-Zadeh, K. (2007). Association between Serum Lipids and Survival in Hemodialysis Patients and Impact of Race. J. Am. Soc. Nephrol. 18: 293-303 [Abstract] [Full Text]  
• Ritz, E., Wanner, C. (2006). Lipid Changes and Statins in Chronic Renal Insufficiency. J. Am. Soc. Nephrol. 17: S226-S230 [Abstract] [Full Text]  
• Goicoechea, M., de Vinuesa, S. G., Lahera, V., Cachofeiro, V., Gomez-Campdera, F., Vega, A., Abad, S., Luno, J. (2006). Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease. J. Am. Soc. Nephrol. 17: S231-S235 [Abstract] [Full Text]  
• Achinger, S. G., Ayus, J. C. (2006). Left Ventricular Hypertrophy: Is Hyperphosphatemia among Dialysis Patients a Risk Factor?. J. Am. Soc. Nephrol. 17: S255-S261 [Abstract] [Full Text]  
• Singh, A. K., Szczech, L., Tang, K. L., Barnhart, H., Sapp, S., Wolfson, M., Reddan, D., the CHOIR Investigators, (2006). Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease. NEJM 355: 2085-2098 [Abstract] [Full Text]  
• Edwards, N.C., Steeds, R.P., Ferro, C.J., Townend, J.N. (2006). The treatment of coronary artery disease in patients with chronic kidney disease. QJM 99: 723-736 [Abstract] [Full Text]  
• Bonovas, S., Filioussi, K., Tsavaris, N., Sitaras, N. M. (2006). Statins and Cancer Risk: A Literature-Based Meta-Analysis and Meta-Regression Analysis of 35 Randomized Controlled Trials. JCO 24: 4808-4817 [Abstract] [Full Text]  
• Hayward, R. A., Hofer, T. P., Vijan, S. (2006). Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem.. ANN INTERN MED 145: 520-530 [Abstract] [Full Text]  
• Habib, A. N., Baird, B. C., Leypoldt, J. K., Cheung, A. K., Goldfarb-Rumyantzev, A. S. (2006). The association of lipid levels with mortality in patients on chronic peritoneal dialysis. Nephrol Dial Transplant 21: 2881-2892 [Abstract] [Full Text]  
• Rakhit, D J, Marwick, T H, Armstrong, K A, Johnson, D W, Leano, R, Isbel, N M (2006). Effect of aggressive risk factor modification on cardiac events and myocardial ischaemia in patients with chronic kidney disease. Heart 92: 1402-1408 [Abstract] [Full Text]  
• Parikh, N. I., Hwang, S.-J., Larson, M. G., Meigs, J. B., Levy, D., Fox, C. S. (2006). Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control.. Arch Intern Med 166: 1884-1891 [Abstract] [Full Text]  
• Moon, J. C, Bogle, R. G (2006). More on switching statins: Authors' reply. BMJ 333: 655-656 [Full Text]  
• Chung, C P, Oeser, A, Avalos, I, Raggi, P, Stein, C M (2006). Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus. Lupus 15: 562-569 [Abstract]  
• Molitch, M. E. (2006). Management of Dyslipidemias in Patients with Diabetes and Chronic Kidney Disease. CJASN 1: 1090-1099 [Abstract] [Full Text]  
• (2006). Statins for primary prevention in type 2 diabetes. DTB 44: 57-60 [Abstract] [Full Text]  
• Moe, S. M., Chertow, G. M. (2006). The Case against Calcium-Based Phosphate Binders. CJASN 1: 697-703 [Abstract] [Full Text]  
• Himmelfarb, J. (2006). Dialysis at a Crossroads: Reverse Engineering Renal Replacement Therapy. CJASN 1: 896-902 [Full Text]  
• Moon, J. C, Bogle, R. G (2006). Switching statins.. BMJ 332: 1344-1345 [Full Text]  
• Jhund, P., McMurray, J. J.V. (2006). Does Aspirin Reduce the Benefit of an Angiotensin-Converting Enzyme Inhibitor?: Choosing Between the Scylla of Observational Studies and the Charybdis of Subgroup Analysis. Circulation 113: 2566-2568 [Full Text]  
• Uhlig, K., Balk, E. M., Lau, J., Levey, A. S. (2006). Clinical Practice Guidelines in nephrology--for worse or for better. Nephrol Dial Transplant 21: 1145-1153 [Full Text]  
• Shanahan, C. M. (2006). Vascular calcification--a matter of damage limitation?. Nephrol Dial Transplant 21: 1166-1169 [Full Text]  
• Son, B.-K., Kozaki, K., Iijima, K., Eto, M., Kojima, T., Ota, H., Senda, Y., Maemura, K., Nakano, T., Akishita, M., Ouchi, Y. (2006). Statins Protect Human Aortic Smooth Muscle Cells From Inorganic Phosphate-Induced Calcification by Restoring Gas6-Axl Survival Pathway. Circ. Res. 98: 1024-1031 [Abstract] [Full Text]  
• Tovar, J. M., Schering, D. B. (2006). Management of Dyslipidemia in Special Populations. Journal of Pharmacy Practice 19: 63-78 [Abstract]  
• Friedman, A., Moe, S. (2006). Review of the Effects of Omega-3 Supplementation in Dialysis Patients. CJASN 1: 182-192 [Abstract] [Full Text]  
• Williams, M. E. (2006). Coronary Revascularization in Diabetic Chronic Kidney Disease/End-Stage Renal Disease: A Nephrologist's Perspective. CJASN 1: 209-220 [Full Text]  
• Stenvinkel, P., Rodriguez-Ayala, E., Massy, Z. A., Qureshi, A. R., Barany, P., Fellstrom, B., Heimburger, O., Lindholm, B., Alvestrand, A. (2006). Statin Treatment and Diabetes Affect Myeloperoxidase Activity in Maintenance Hemodialysis Patients. CJASN 1: 281-287 [Abstract] [Full Text]  
• Kasiske, B. L., Maclean, J. R., Snyder, J. J. (2006). Acute Myocardial Infarction and Kidney Transplantation. J. Am. Soc. Nephrol. 17: 900-907 [Abstract] [Full Text]  
• (2006). Additional articles abstracted in ACP Journal Club. Evid. Based Med. 11: 30-30 [Full Text]  
• Panichi, V., Paoletti, S., Mantuano, E., Manca-Rizza, G., Filippi, C., Santi, S., Taccola, D., Donadio, C., Tramonti, G., Innocenti, M., Casto, G., Consani, C., Sbragia, G., Franzoni, F., Galetta, F., Panicucci, E., Barsotti, G. (2006). In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients. Nephrol Dial Transplant 21: 337-344 [Abstract] [Full Text]  
• Ginsberg, H. N. (2006). REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia. J. Clin. Endocrinol. Metab. 91: 383-392 [Abstract] [Full Text]  
• Dale, K. M., Coleman, C. I., Henyan, N. N., Kluger, J., White, C. M. (2006). Statins and Cancer Risk: A Meta-analysis. JAMA 295: 74-80 [Abstract] [Full Text]  
• Berl, T., Henrich, W. (2006). Kidney-Heart Interactions: Epidemiology, Pathogenesis, and Treatment. CJASN 1: 8-18 [Full Text]  
• Prepared by: British Cardiac Society, British Hype, (2005). JBS 2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 91: v1-v52 [Full Text]  
• Tonelli, M., Keech, A., Shepherd, J., Sacks, F., Tonkin, A., Packard, C., Pfeffer, M., Simes, J., Isles, C., Furberg, C., West, M., Craven, T., Curhan, G. (2005). Effect of Pravastatin in People with Diabetes and Chronic Kidney Disease. J. Am. Soc. Nephrol. 16: 3748-3754 [Abstract] [Full Text]  
• Dennis, V. W. (2005). Coronary Heart Disease in Patients with Chronic Kidney Disease. J. Am. Soc. Nephrol. 16: S103-S106 [Full Text]  
• Langer, A., Robinson, J. G., Jaber, B. L., Madias, N. E., Wanner, C., Krane, V., Ritz, E. (2005). Atorvastatin in patients with type 2 diabetes mellitus undergoing dialysis.. NEJM 353: 1858-1860 [Full Text]  
• (2005). JournalScan. Heart 91: 1375-1376 [Full Text]  
• (2005). Statin Trial in Diabetic Patients on Hemodialysis. Journal Watch Cardiology 2005: 4-4 [Full Text]  
• Tonks, A. (2005). What's new in the other general journals. BMJ 331: 257-258 [Full Text]